The ability to manipulate the germline of the laboratory mouse has revolutionized the study of complex processes such as embryo development and disease in vertebrates. The use of novel mutant mouse strains has become a cornerstone in the research efforts of the CCR. To date, CCR members have generated more than 150 mutant mouse strains and several CCR laboratories have a world-renowned reputation in designing increasingly sophisticated techniques to produce mouse models that closely phenocopy a particular human disease. This includes custom designing mutations in mice that mimic the exact mutations seen in cancer patients and utilizing newly developed lentivirus-mediated transgenesis to allow rapid screening of transgenic [unreadable]knockdown[unreadable] phenotypes. The objective of the Transgenic Animal Core Facility is to make transgenic, genetargeting and lentivirus-mediated transgenesis technologies accessible to all CCR laboratories regardless of their previous experience with the generation and analysis of mouse models. The facility conducts a variety of procedures on a fee-for-service basis including (1) gene targeting and expansion of ES cell lines, (2) culture of ES cells for analysis, (3) ES cell karyotyping, (4) injection of ES cells into blastocysts, (5) pronuclear injections of either classic transgenic vectors or lentiviruses, and (6) surgical implantation of blastocyts and maintenance of chimeras until weaning. The centralization of these services maximizes the efficiency and cost effectiveness of generating mutant mouse models and also relieves CCR researchers from the need to learn these procedures. However, the facility places equal emphasis on investigator education and will provide state of the art training to CCR researchers in any or all the procedures required to create targeted ES cells, transgenics, and mutant mouse models. Finally, the facility maintains a growing collection of various reagent mice, for example strains expressing Cre or Flp recombinase under tissue-specific or inducible promoters, which are available to CCR Investigators for a small charge.